Photobiomodulation for Alzheimer’s Disease: Translating Basic Research to Clinical Application

Abstract

One of the challenges in translating new therapeutic approaches to the patient bedside lies in bridging the gap between scientists who are conducting basic laboratory research and medical practitioners who are not exposed to highly specialized journals. This review covers the literature on photobiomodulation therapy as a novel approach to prevent and treat Alzheimer's disease, aiming to bridge that gap by gathering together the terms and technical specifications into a single concise suggestion for a treatment protocol. In light of the predicted doubling in the number of people affected by dementia and Alzheimer's disease within the next 30 years, a treatment option which has already shown promising results in cell culture studies and animal models, and whose safety has already been proven in humans, must not be left in the dark. This review covers the mechanistic action of photobiomodulation therapy against Alzheimer's disease at a cellular level. Safe and effective doses have been found in animal models, and the first human case studies have provided reasons to undertake large-scale clinical trials. A brief discussion of the minimally effective and maximum tolerated dose concludes this review, and provides the basis for a successful translation from bench to bedside.

Phototherapy for Cognitive Function in Patients With Dementia: A Systematic Review and Meta-Analysis

“…Phototherapy may be a novel non-pharmacological intervention for improving the cognitive symptoms of dementia. The light types of phototherapy can be broadly categorized into bright and near-infrared (NIR) light and can be more finely divided into light-emitting diodes (LEDs) and lasers (Enengl et al, 2020). Photobiomodulation (PBM), an emerging technology, refers specifically to neuromodulation via transcranial phototherapy, which is different from the conventional light therapy mediated by environmental changes (Hamblin, 2019).…”

Near-infrared light reduces glia activation and modulates neuroinflammation in the brains of diet-induced obese mice

“… 50 , 60 , 111 , 138 , 139 Previous studies have shown that NIR decreases brain levels of the main anti-inflammatory cytokines (IL-1β and TNF-α) and reduces glia activation in different models of TBI and AD 59 , 61 , 92 , 93 , 111 – 113 , 127 , 132 , 135 , 136 , 140 – 142 . Likewise, NIR upregulates BDNF in rodent injury models and in animal models that develop neuroinflammation, suggesting that it may provide neuronal and synaptic protection 92 , 93 , 135 , 136 , 142 .…”

“…This study did not explore mechanistic pathways to ascertain the anti-inflammatory effect of NIR; rather we sought to establish whether NIR can be a preventative treatment for conditions known to pose serious threats to CNS integrity 59,60,137 . 50,60,111,138,139 Previous studies have shown that NIR decreases brain levels of the main anti-inflammatory cytokines (IL-1β and TNF-α) and reduces glia activation in different models of TBI and AD 59,61,92,93,[111][112][113]127,132,135,136,[140][141][142] . Likewise, NIR upregulates BDNF in rodent injury models and in animal models that develop neuroinflammation, suggesting that it may provide neuronal and synaptic protection 92,93,135,136,142 .…”

“…50,60,111,138,139 Previous studies have shown that NIR decreases brain levels of the main anti-inflammatory cytokines (IL-1β and TNF-α) and reduces glia activation in different models of TBI and AD 59,61,92,93,[111][112][113]127,132,135,136,[140][141][142] . Likewise, NIR upregulates BDNF in rodent injury models and in animal models that develop neuroinflammation, suggesting that it may provide neuronal and synaptic protection 92,93,135,136,142 . Given the paramount importance of BDNF in maintaining synapse function and integrity, we hypothesize that NIR-induced upregulation in the hippocampus may restore or improve synaptic transmission and neuronal plasticity, with beneficial effects on memory and learning processes.…”

“…In light of our results, we speculate that NIR may be further developed as a protective treatment for subjects with obesity, diabetes, or metabolic syndrome who are at high risk of developing dementia. Several recent studies and clinical trials have successfully used transcranial NIR delivery in patients with AD and other neurologic and neurodegenerative disorders such as depression, PD and TBI 58,61,142,143 , and it has been shown to improve cognitive performance in normal subjects [144][145][146] . We consider this approach a valid strategy as a preventative treatment for dementia and AD, especially for individuals who are obese and/or insulin-resistant/diabetic and therefore at high risk of developing cognitive dysfunction later in life.…”